cytidine diphosphate choline

Summary

Summary: Donor of choline in biosynthesis of choline-containing phosphoglycerides.

Top Publications

  1. Teather L, Wurtman R. Dietary cytidine (5')-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:711-7 pubmed
    ..These findings suggest that early-aged rats display a selective impairment in hippocampal-dependent long-term memory, and that dietary CDP-choline supplementation can protect against this deficit...
  2. Conant R, Schauss A. Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Altern Med Rev. 2004;9:17-31 pubmed
    ..This review, while not intended to be exhaustive, highlights the published, peer-reviewed research on citicoline with brief discussions on toxicology and safety, mechanisms of action, and pharmacokinetics...
  3. Blount P, Nguyen C, McDeavitt J. Clinical use of cholinomimetic agents: a review. J Head Trauma Rehabil. 2002;17:314-21 pubmed
  4. Hurtado O, Cardenas A, Pradillo J, Morales J, Ortego F, Sobrino T, et al. A chronic treatment with CDP-choline improves functional recovery and increases neuronal plasticity after experimental stroke. Neurobiol Dis. 2007;26:105-11 pubmed
  5. Zafonte R, Friedewald W, Lee S, Levin B, Diaz Arrastia R, Ansel B, et al. The citicoline brain injury treatment (COBRIT) trial: design and methods. J Neurotrauma. 2009;26:2207-16 pubmed publisher
    ..Secondary outcomes include survival, toxicity, and rate of recovery...
  6. Davalos A, Castillo J, Alvarez Sabin J, Secades J, Mercadal J, Lopez S, et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke. 2002;33:2850-7 pubmed
  7. Rao A, Hatcher J, Dempsey R. Lipid alterations in transient forebrain ischemia: possible new mechanisms of CDP-choline neuroprotection. J Neurochem. 2000;75:2528-35 pubmed
  8. Gunstad J, Brickman A, Paul R, Browndyke J, Moser D, Ott B, et al. Progressive morphometric and cognitive changes in vascular dementia. Arch Clin Neuropsychol. 2005;20:229-41 pubmed
    ..Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact...
  9. Cohen R, Browndyke J, Moser D, Paul R, Gordon N, Sweet L. Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes. Cerebrovasc Dis. 2003;16:199-204 pubmed
    b>Cytidine diphosphate choline (citicoline) has been previously shown to have efficacy in reducing the functional impairments associated with acute stroke...

More Information

Publications61

  1. Adibhatla R, Hatcher J, Dempsey R. Cytidine-5'-diphosphocholine affects CTP-phosphocholine cytidylyltransferase and lyso-phosphatidylcholine after transient brain ischemia. J Neurosci Res. 2004;76:390-6 pubmed
    ..01 compared to saline). These data indicate that PtdCho synthesis is impaired after brain ischemia, and CDP-choline may increase PtdCho levels by attenuating the loss of CCT activity and lyso-PtdCho formation...
  2. Crespo D, Megias M, Fernandez Viadero C, Verduga R. Chronic treatment with a precursor of cellular phosphatidylcholine ameliorates morphological and behavioral effects of aging in the mouse [correction of rat] hippocampus. Ann N Y Acad Sci. 2004;1019:41-3 pubmed
    ..Experimental observations suggest that CDP-choline has a positive effect on memory (reference errors were attenuated), and hippocampal morphology resembled that of younger animals...
  3. Grieb P, Gadamski R, Wojda R, Janisz M. CDP-choline, but not cytidine, protects hippocampal CA1 neurones in the gerbil following transient forebrain ischaemia. Folia Neuropathol. 2001;39:141-5 pubmed
    ..The choline moiety of CDP-choline appears to be essential for the neuroprotective properties of the drug...
  4. Wurtman R, Regan M, Ulus I, Yu L. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol. 2000;60:989-92 pubmed
    ..Hence, it seems likely that the circulating substrates through which oral citicoline increases membrane phosphatide synthesis in the brains of humans involve uridine and choline, and not cytidine and choline as in rats...
  5. McDaniel M, Maier S, Einstein G. "Brain-specific" nutrients: a memory cure?. Nutrition. 2003;19:957-75 pubmed
    ..The compounds examined are phosphatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antioxidants (particularly vitamin E)...
  6. Sweet L, Paul R, Cohen R, Moser D, Ott B, Gordon N, et al. Neuroimaging correlates of dementia rating scale performance at baseline and 12-month follow-up among patients with vascular dementia. J Geriatr Psychiatry Neurol. 2003;16:240-4 pubmed
    ..These findings indicate that although SH volume increases with disease progression, the relative impact of SH volume on cognitive status decreases among patients with advanced VaD...
  7. Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F. Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?. J Neurol Sci. 2007;257:264-9 pubmed
    ..However, they probably would justify reconsideration of the most promising molecules in larger carefully controlled studies...
  8. Clark W. Efficacy of citicoline as an acute stroke treatment. Expert Opin Pharmacother. 2009;10:839-46 pubmed
    ..Citicoline clinical efficacy trials are now continuing outside of the US in both ischemic and hemorrhagic stroke. A citicoline supplement is now available from several sources on the internet...
  9. Paul R, Cohen R, Moser D, Ott B, Sethi M, Sweet L, et al. Clinical correlates of cognitive decline in vascular dementia. Cogn Behav Neurol. 2003;16:40-6 pubmed
    ..To determine whether demographic data, dementia severity, functional status, whole brain volume (WBV), or subcortical hyperintensity volume (SH) predict subsequent cognitive decline in vascular dementia (VaD)...
  10. Saver J. Citicoline: update on a promising and widely available agent for neuroprotection and neurorepair. Rev Neurol Dis. 2008;5:167-77 pubmed
    ..Reinvestigation of citicoline with modern neuroimaging and clinical trial methods are underway and will provide more definitive information regarding the mechanistic and clinical effects of this promising neurotherapeutic agent...
  11. García Cobos R, Frank Garcia A, Gutiérrez Fernández M, Diez Tejedor E. Citicoline, use in cognitive decline: vascular and degenerative. J Neurol Sci. 2010;299:188-92 pubmed publisher
    ..The use of new neuroimaging procedures in current trials could be of great interest...
  12. Secades J. Citicoline: pharmacological and clinical review, 2010 update. Rev Neurol. 2011;52 Suppl 2:S1-S62 pubmed
    ..There are retrieved the most important experimental and clinical data in both indications...
  13. Secades J, Alvarez Sabin J, Rubio F, Lozano R, Davalos A, Castillo J. Citicoline in intracerebral haemorrhage: a double-blind, randomized, placebo-controlled, multi-centre pilot study. Cerebrovasc Dis. 2006;21:380-5 pubmed
    ..Citicoline is a neuroprotectant drug with some beneficial effects in human ischaemic stroke and with an excellent safety profile. We decided to carry out a pilot study to test its safety and efficacy in human intracerebral haemorrhaging...
  14. Cho H, Kim Y. Efficacy and safety of oral citicoline in acute ischemic stroke: drug surveillance study in 4,191 cases. Methods Find Exp Clin Pharmacol. 2009;31:171-6 pubmed publisher
    ..62%), followed by gastrointestinal symptoms (5 of 37, 13.5%). Oral citicoline improved neurological, functional and global outcomes in patients with acute ischemic stroke without significant safety concerns...
  15. Clark W, Williams B, Selzer K, Zweifler R, Sabounjian L, Gammans R. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke. 1999;30:2592-7 pubmed
    ..A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects...
  16. Teather L, Wurtman R. Dietary CDP-choline supplementation prevents memory impairment caused by impoverished environmental conditions in rats. Learn Mem. 2005;12:39-43 pubmed
  17. Barrachina M, Dominguez I, Ambrosio S, Secades J, Lozano R, Ferrer I. Neuroprotective effect of citicoline in 6-hydroxydopamine-lesioned rats and in 6-hydroxydopamine-treated SH-SY5Y human neuroblastoma cells. J Neurol Sci. 2003;215:105-10 pubmed
    ..Finally, citicoline significantly attenuates substantia nigra (SN) dopaminergic cell dropout and tyrosine hydroxylase immunoreactivity in the ipsilateral striatum in rats injected intrastriatally with 6-hydroxydopamine (6-OHDA)...
  18. Abad Santos F, Novalbos Reina J, Gallego Sandín S, Garcia A. [Treatment of mild cognitive impairment: value of citicoline]. Rev Neurol. 2002;35:675-82 pubmed
    ..The aim of this study is to evaluate whether citilcoline can be effective in this clinical situation...
  19. Alvarez Sabin J, Roman G. Citicoline in vascular cognitive impairment and vascular dementia after stroke. Stroke. 2011;42:S40-3 pubmed publisher
  20. Alvarez X, Mouzo R, Pichel V, Perez P, Laredo M, Fernandez Novoa L, et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol. 1999;21:633-44 pubmed
  21. Clark W, Gunion Rinker L, Lessov N, Hazel K. Citicoline treatment for experimental intracerebral hemorrhage in mice. Stroke. 1998;29:2136-40 pubmed
    ..The present study was designed to test whether treatment with citicoline reduces ischemic injury and improves functional neurological outcome in an experimental model of ICH...
  22. Adibhatla R, Hatcher J. Citicoline mechanisms and clinical efficacy in cerebral ischemia. J Neurosci Res. 2002;70:133-9 pubmed
    ..The clinical efficacy of citicoline should be examined further in light of the recent phase III stroke clinical trials and experimental data for cerebral ischemia...
  23. Secades J. Probably role of citicoline in stroke rehabilitation: review of the literature. Rev Neurol. 2012;54:173-9 pubmed
    ..In this context, the role of citicoline in the rehabilitation of patients with stroke is reviewed...
  24. Secades J, Lorenzo J. Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol. 2006;28 Suppl B:1-56 pubmed
    ..No serious side effects have occurred in any series of patients treated with citicoline, which attests to the safety of treatment with citicoline...
  25. Fernández Murray J, McMaster C. Glycerophosphocholine catabolism as a new route for choline formation for phosphatidylcholine synthesis by the Kennedy pathway. J Biol Chem. 2005;280:38290-6 pubmed
  26. Bettini R, Gorini M. [Reaction times during citicoline treatment]. Clin Ter. 2002;153:247-50 pubmed
    ..Better results were obtained in patients who received two cycles of therapy. No side effects were observed during the study...
  27. Putignano S, Gareri P, Castagna A, Cerqua G, Cervera P, Cotroneo A, et al. Retrospective and observational study to assess the efficacy of citicoline in elderly patients suffering from stupor related to complex geriatric syndrome. Clin Interv Aging. 2012;7:113-8 pubmed publisher
    ..We have evaluated the administration of citicoline in geriatric patients following a protocol of intravenous study on improvement of individual performances...
  28. Adibhatla R, Hatcher J. Cytidine 5'-diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res. 2005;30:15-23 pubmed
    ..CDP-choline is non-xenobiotic, safe, well tolerated, and can be considered as one of the agents in multi-drug treatment of stroke...
  29. Hurtado O, Lizasoain I, Moro M. Neuroprotection and recovery: recent data at the bench on citicoline. Stroke. 2011;42:S33-5 pubmed publisher
    ..Furthermore, citicoline stimulates neuronal plasticity and improves sensorimotor recovery in the chronic phase of experimental stroke...
  30. Hurtado O, Moro M, Cárdenas A, Sanchez V, Fernández Tomé P, Leza J, et al. Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis. 2005;18:336-45 pubmed
    ..The present study was designed to search for mechanisms of citicoline neuroprotective properties using in vivo and in vitro models of brain ischemia...
  31. Cavun S, Savci V. CDP-choline increases plasma ACTH and potentiates the stimulated release of GH, TSH and LH: the cholinergic involvement. Fundam Clin Pharmacol. 2004;18:513-23 pubmed
    ..Both muscarinic and nicotinic receptor activations, separately, mediated the increases in serum GH and LH levels after CDP-choline...
  32. Shen Z. Brain cholinesterases: III. Future perspectives of AD research and clinical practice. Med Hypotheses. 2004;63:298-307 pubmed
    ..Their working mechanisms may be through directly changing the configuration of AChE molecules and/or correcting micro- and overall environmental biological conditions for ChEs...
  33. Gutiérrez Fernández M, Rodríguez Frutos B, Fuentes B, Vallejo Cremades M, Alvarez Grech J, Expósito Alcaide M, et al. CDP-choline treatment induces brain plasticity markers expression in experimental animal stroke. Neurochem Int. 2012;60:310-7 pubmed publisher
    ..In fact, CDP-choline increased cell proliferation, vasculogenesis and synaptophysin levels and reduced GFAP levels in the peri-infarct area of the ischemic stroke...
  34. Wang L, Rouleau D, Beaumont E. Most effective adjuvant treatments after surgery in peripheral nerve laceration: Systematic review of the literature on rodent models. Restor Neurol Neurosci. 2013;31:253-62 pubmed publisher
    ..Animal studies, comparing treatments administered within the same experimental protocol, are needed to truly assess efficiency and to provide solid recommendations for future clinical investigation...
  35. Hjelmstad R, Bell R. sn-1,2-diacylglycerol choline- and ethanolaminephosphotransferases in Saccharomyces cerevisiae. Mixed micellar analysis of the CPT1 and EPT1 gene products. J Biol Chem. 1991;266:4357-65 pubmed
    ..These studies provide the first definitive kinetic properties of individual choline- and ethanolaminephosphotransferases...
  36. Tsukagoshi Y, Nikawa J, Yamashita S. Molecular cloning and characterization of the gene encoding cholinephosphate cytidylyltransferase in Saccharomyces cerevisiae. Eur J Biochem. 1987;169:477-86 pubmed
    ..coli) and DNA ligase (T4 phage), suggesting that these five enzymes are evolutionarily related. Statistically significant sequence homology was also noted between the human c-fos gene product and the enzyme...
  37. Mievis S, Levivier M, Vassart G, Brotchi J, Ledent C, Blum D. Citicoline is not protective in experimental models of Huntington's disease. Neurobiol Aging. 2007;28:1944-6 pubmed
    ..Altogether, our results suggest that citicoline is not a potential therapeutic agent for the treatment of Huntington's disease...
  38. Kulinski A, Vance D, Vance J. A choline-deficient diet in mice inhibits neither the CDP-choline pathway for phosphatidylcholine synthesis in hepatocytes nor apolipoprotein B secretion. J Biol Chem. 2004;279:23916-24 pubmed
    ..Moreover, the amount and m activity of the cytidylyltransferase and methyltransferase were increased. The reduction in plasma apoB in mice deprived of dietary choline cannot, therefore, be attributed to decreased apoB secretion...
  39. Yu Y, Sreenivas A, Ostrander D, Carman G. Phosphorylation of Saccharomyces cerevisiae choline kinase on Ser30 and Ser85 by protein kinase A regulates phosphatidylcholine synthesis by the CDP-choline pathway. J Biol Chem. 2002;277:34978-86 pubmed
    ..These data supported the conclusion that phosphorylation of choline kinase on Ser(30) and Ser(85) by protein kinase A regulates PC synthesis by the CDP-choline pathway...
  40. Mancini A, Del Rosso F, Roberti R, Orvietani P, Coletti L, Binaglia L. Purification of ethanolaminephosphotransferase from bovine liver microsomes. Biochim Biophys Acta. 1999;1437:80-92 pubmed
    ..Mg2+-dependent CDP-choline:diacylglycerol cholinephosphotransferase (EC 2.7.8.2) is completely inactivated during the solubilization and purification steps...
  41. Fiedorowicz M, Makarewicz D, Stańczak Mrozek K, Grieb P. CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia. Acta Neurobiol Exp (Wars). 2008;68:389-97 pubmed
    ..In the context of the well-known excellent safety profile of citicoline, these data suggest that clinical evaluation of the efficacy of the drug in human birth asphyxia may be warranted...
  42. Bracken B, Penetar D, Rodolico J, Ryan E, Lukas S. Eight weeks of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults. Pharmacol Biochem Behav. 2011;98:518-24 pubmed publisher
    ..Therefore, it is important to know the impact of citicoline on the sleep/wake cycle in these individuals in order to rate its overall efficacy...
  43. Martin J, Bakker Grunwald T, Klein G. 31P-NMR analysis of Entamoeba histolytica. Occurrence of high amounts of two inositol phosphates. Eur J Biochem. 1993;214:711-8 pubmed
    ..These components were identified by 31P-NMR, using homonuclear J-resolved and two-dimensional 1H-31P correlative, analyses as myo-inositol trisphosphate, Ins(2,4,6)P3, and pentakisphospho-myo-inositol diphosphate, Ins(1,2,3,4,6)P5(5)P2...
  44. Ross B, Mamalias N, Moszczynska A, Rajput A, Kish S. Elevated activity of phospholipid biosynthetic enzymes in substantia nigra of patients with Parkinson's disease. Neuroscience. 2001;102:899-904 pubmed
    ..We suggest that pharmacotherapies which augment this compensatory response might have utility as a treatment for Parkinson's disease...
  45. Eyigor O, Coskun C, Cavun S, Savci V. Intravenous CDP-choline activates neurons in supraoptic and paraventricular nuclei and induces hormone secretion. Brain Res Bull. 2012;87:286-94 pubmed publisher
    ..Results of the present study suggested that peripheral administration of CDP-choline is able to increase plasma oxytocin and vasopressin levels while activating the respective neurons...
  46. Sahota P, Savitz S. Investigational therapies for ischemic stroke: neuroprotection and neurorecovery. Neurotherapeutics. 2011;8:434-51 pubmed publisher
    ..In this review, we highlight select pharmacologic and cell-based therapies that are currently in the clinical trial stage for stroke...
  47. Paul R, Cohen R, Moser D, Ott B, Zawacki T, Gordon N. Performance on the Hooper Visual Organizational Test in patients diagnosed with subcortical vascular dementia: relation to naming performance. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14:93-7 pubmed
    ..To examine the performance of individuals with vascular dementia (VaD) on the Hooper Visual Organization Test (HVOT) and to determine the influence of naming on HVOT performance in this population...
  48. Xu K, Xiong Y, Du Y. Argipressin(4-8) upregulate CTP: phosphocholine cytidylyltransferase in rat hippocampal neurons. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2002;34:418-22 pubmed
    ..Meanwhile, AVP(4-8) could also increase CCT activity in rat hippocampal neurons. These results demonstrated that AVP(4-8) upregulated CCT mRNA level and its activity through stabilizing the CCT mRNA in rat hippocampal neurons...
  49. Witola W, Ben Mamoun C. Choline induces transcriptional repression and proteasomal degradation of the malarial phosphoethanolamine methyltransferase. Eukaryot Cell. 2007;6:1618-24 pubmed
    ..These data provide the first evidence for metabolite-mediated transcriptional and proteasomal regulation in Plasmodium and will set the stage for the use of this system for conditional gene and protein expression in this organism...
  50. Ozay R, Bekar A, Kocaeli H, Karli N, Filiz G, Ulus I. Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats. Surg Neurol. 2007;68:615-22; discussion 622 pubmed
    ..Citicoline has been shown to have beneficial effects in a variety of CNS injury models. The aim of this study was to test the effects of citicoline on nerve regeneration and scarring in a rat model of peripheral nerve surgery...
  51. Ohkawa Y, Kiyohara Y, Asoh T, Maeda H, Kurumi M, Sasaki K, et al. Application of 4-hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter. Biol Pharm Bull. 2001;24:1404-10 pubmed
    ..The increment in the drug distribution to the brain with the concomitant use of 4-OH (or APAPS) observed in this study is useful information for the application of drug combinations as biodistribution promoters...
  52. Diederich K, Frauenknecht K, Minnerup J, Schneider B, Schmidt A, Altach E, et al. Citicoline enhances neuroregenerative processes after experimental stroke in rats. Stroke. 2012;43:1931-40 pubmed publisher
    ..Our present study was designed to check whether citicoline also enhances neuroregeneration after experimental stroke...